Supplementary Table 3: Selected anti-angiogenesis clinical trials in the metastatic setting.

Agent / Randomized trial / Response / Reference
Colorectal cancer
Irinotecan, fluorouracil leucovorin (IFL) + Bevacizumab
(Previously untreated patients) / Yes / Survival 20.3 mo (IFL-B) vs 15.6 mo (IFL) / Hurwitz et al. (2004)1
Flurouracil, leucovorin (FU/LV)+ Bevacizumab(Previously untreated patients)
Combined analysis / Yes / Survival 17.9 mo FU/LV-B
Survival 14.6 mo FU/LV / Kabbinavar et al. (2005)2
Fluorouracil, leucovorinBevacizumab (patients previously progressed on irinotecan, and oxaliplatin) / No / ORR 1% / Chen et al. (2006)3
Oxaliplatin, fluorouracil, leucovorin(FOLFOX4) + Bevacizumab
(Previously progressed on fluoropyrimidine and irinotecan) / Yes / Survival 12.9 mo (FOLFOX4-B)
Survival 10.8 mo (FOLFOX4)
Survival 10.2 mo Bevacizumab / Giantonio et al. (2007)4
Non-small-cell lung cancer
Paclitaxel, Carboplatin (PC) + Bevacizumab / Yes / Survival 12.3 mo (BPC) vs 10.3 mo (PC) / Sandler et al. (2006)5
Bevacizumab, Erlotinib( one prior chemotherapy) / No / ORR 20%
SD 65% / Herbst et al. (2005)6
Renal cell carcinoma
Bevacizumab vs placebo / Yes / TTP in high-dose Bev vs placebo, P<0.001
TTP in low dose Bev vs placebo, P = 0.053
Survival, NS / Yang et al. (2003)7
Sorafenib vs placebo / Yes / PFS Sorafenib 5.5 mo vs placebo 2.8 mo
Survival hazard ratio 0.72, NS / Escudier et al. (2007)8
Sunitinib vs Interferon-alfa (IFN) / Yes / ORR: Sunitinib 31%, IFN 6%
PFS: Sunitinib 11 mo, IFN 5 mo / Motzer et al. (2007)9
Bevacizumab, Erlotinib / No / ORR: 25%
SD (8 weeks) 61% / Hainsworth et al. (2005)10
Hepatocellular carcinoma
Gemcitabine, Oxaliplatin (GO) + Bevacizumab / No / ORR 20%, SD 27% / Zhu et al. (2006)11
Pancreatic cancer
Gemcitabine, Bevacizumab (Previously untreated patients) / No / ORR 21%, SD 46% / Kindler et al. (2005)12
Breast cancer
Capecitabine + Bevacizumab (Patients previously treated with an anthracycline and taxane) / Yes / ORR 19.8% (C-B)
vs 9.1% (C)
Survival NS / Miller et al. (2005)13
Docetaxel, Bevacizumab (First- or second-line therapy) / No / ORR 52%
SD 33% / Ramaswamy et al. (2006)14
ZD6474
Refractory disease / No / ORR 0%
SD 2% / Miller et al. (2005)15
Unknown primary site
Bevacizumab, Erlotinib / No / ORR 10%
SD 61% / Hainsworth et al. (2007)16

Abbreviations: B, bevacizumab; NS, not significant; ORR, objective response rate; PFS, progression-free survival; TTP, time to progression.

References

1Hurwitz Het al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med350: 2335–2342

2Kabbinavar FFet al. (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol23: 3706–3712

3Chen HXet al. (2006) Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol24, 3354–3360

4Giantonio BJet al. (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol25: 1539–1544

5Sandler Aet al. (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med355: 2542–2550

6Herbst RSet al. (2005) Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol23: 2544–2555

7Yang JCet al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med349: 427–434

8Escudier B et al. (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med356: 125–134

9Motzer RJet al. (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med356: 115–124

10Hainsworth JDet al. (2005) Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol23: 7889–7896

11Zhu AXet al. (2006) Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol24: 1898–1903

12Kindler HLet al. (2005) Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol23: 8033–8040

13Miller KDet al. (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol23: 792–799

14Ramaswamy Bet al. (2006) Phase II trial of bevacizumab in combination with weekly docetaxel in metastatic breast cancer patients. Clin Cancer Res12: 3124–3129

15Miller KDet al. (2005) A multicenter phase II trial of ZD6474, a vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinase inhibitor, in patients with previously treated metastatic breast cancer. Clin Cancer Res11: 3369–3376

16Hainsworth JDet al. (2007) Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network. J Clin Oncol25: 1747–1752